Deletion of the Cl-/HCO3- exchanger pendrin downregulates calcium-absorbing proteins in the kidney and causes calcium wasting.
Nephrol Dial Transplant
; 27(4): 1368-79, 2012 Apr.
Article
em En
| MEDLINE
| ID: mdl-21873623
ABSTRACT
BACKGROUND:
The epithelial calcium channel (ECaC) (TRPV5) and the Cl-/HCO3- exchanger pendrin (SLC26A4) are expressed on the apical membrane of tubular cells in the distal nephron and play essential roles in calcium re-absorption and bicarbonate secretion, respectively, in the kidney.METHODS:
A combination of functional and molecular biology techniques were employed to examine the role of pendrin deletion in calcium excretion.RESULTS:
Here, we demonstrate that deletion of pendrin causes acidic urine [urine pH 4.9 in knockout (KO) versus 5.9 in wild-type (WT) mice, P<0.03)] and downregulates the calcium-absorbing molecules ECaC and Na/Ca exchanger in the kidney, as shown by northern hybridization, immunoblot analysis and/or immunofluorescent labeling. These changes were associated with a â¼100% increase in 24-h urine calcium excretion in pendrin null mice. Subjecting the pendrin WT and KO mice to oral bicarbonate loading for 12 days increased the urine pH to â¼8 in both genotypes, normalized the expression of ECaC and Na/Ca exchanger and reduced the urine calcium excretion in pendrin-null mice to levels comparable to WT mice.CONCLUSIONS:
We suggest that pendrin dysfunction should be suspected and investigated in humans with an otherwise unexplained acidic urine and hypercalciuria.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Canais de Cálcio
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Cálcio
/
Trocador de Sódio e Cálcio
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Proteínas de Transporte de Ânions
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Antiportadores de Cloreto-Bicarbonato
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Canais de Cátion TRPV
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Rim
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article